1. Field of the Invention
The present invention relates generally to the fields of protein biology, immunology and oncology. More particularly, it concerns predicting the response of a patient to anti-CD20 antibody therapy by assessing a C1qA genotype.
2. Description of Related Art
Anti-tumor antibodies can impede tumor growth and spreading by inducing complement-mediated lysis (Gelderman et al., 2004; Harjunpaa et al., 2000; Hakulinen and Meri, 1998), mediating antibody-dependent cellular cytotoxicity (Eccles, 2001), or directly triggering cell cycle arrest and apoptosis of tumor cells (Racila et al., 1995). In vitro and animal model studies suggest that complement factors and complement inhibitors can amend the immune response to tumors, and could be important in determining the response to cancer immunotherapy (Caragine et al., 2002a; Fishelson et al., 2003; Caragine et al., 2002b; Jurianz et al., 1999; Golay et al., 2000). Complement fractions may also play an indirect role in cell-mediated cytotoxicity by recruiting the effector cells at the site of inflammation, infection or tumor development (Tazawa et al., 2003; Baldwin et al., 1999; Onoe et al., 2002).
The complement system is a key component of the immune response, and can contribute to the anti-tumor immune response (Hakulinen and Meri, 1998). A number of reports indicate that the ability of cancer to escape complement-induced lysis correlates with expression of membrane-bound complement regulatory proteins (Fishelson et al., 2003; Gorter and Meri, 1999; Donin et al., 2003). ADCC activity can be enhanced by complement receptor 3 binding to iC3b, a product of early complement activation starting with C1q in the presence of tumor specific antibody, thus enhancing FcγR-mediated effector-cell binding (Gelderman et al., 2004). However, little is known about whether heterogeneity in the host's complement system itself has an impact on anti-tumor immunity.